TU Darmstadt / ULB / TUbiblio

Polo-like kinase 3 regulates CtIP during DNA double-strand break repair in G1.

Barton, Olivia and Naumann, Steffen C. and Diemer-Biehs, Ronja and Künzel, Julia and Steinlage, Monika and Conrad, Sandro and Makharashvili, Nodar and Wang, Jiadong and Feng, Lin and Lopez, Bernard S. and Paull, Tanya T. and Chen, Junjie and Jeggo, Penny A. and Löbrich, Markus :
Polo-like kinase 3 regulates CtIP during DNA double-strand break repair in G1.
In: The Journal of cell biology, 206 (7) pp. 877-94. ISSN 1540-8140
[Article] , (2014)

Abstract

DNA double-strand breaks (DSBs) are repaired by nonhomologous end joining (NHEJ) or homologous recombination (HR). The C terminal binding protein-interacting protein (CtIP) is phosphorylated in G2 by cyclin-dependent kinases to initiate resection and promote HR. CtIP also exerts functions during NHEJ, although the mechanism phosphorylating CtIP in G1 is unknown. In this paper, we identify Plk3 (Polo-like kinase 3) as a novel DSB response factor that phosphorylates CtIP in G1 in a damage-inducible manner and impacts on various cellular processes in G1. First, Plk3 and CtIP enhance the formation of ionizing radiation-induced translocations; second, they promote large-scale genomic deletions from restriction enzyme-induced DSBs; third, they are required for resection and repair of complex DSBs; and finally, they regulate alternative NHEJ processes in Ku(-/-) mutants. We show that mutating CtIP at S327 or T847 to nonphosphorylatable alanine phenocopies Plk3 or CtIP loss. Plk3 binds to CtIP phosphorylated at S327 via its Polo box domains, which is necessary for robust damage-induced CtIP phosphorylation at S327 and subsequent CtIP phosphorylation at T847.

Item Type: Article
Erschienen: 2014
Creators: Barton, Olivia and Naumann, Steffen C. and Diemer-Biehs, Ronja and Künzel, Julia and Steinlage, Monika and Conrad, Sandro and Makharashvili, Nodar and Wang, Jiadong and Feng, Lin and Lopez, Bernard S. and Paull, Tanya T. and Chen, Junjie and Jeggo, Penny A. and Löbrich, Markus
Title: Polo-like kinase 3 regulates CtIP during DNA double-strand break repair in G1.
Language: English
Abstract:

DNA double-strand breaks (DSBs) are repaired by nonhomologous end joining (NHEJ) or homologous recombination (HR). The C terminal binding protein-interacting protein (CtIP) is phosphorylated in G2 by cyclin-dependent kinases to initiate resection and promote HR. CtIP also exerts functions during NHEJ, although the mechanism phosphorylating CtIP in G1 is unknown. In this paper, we identify Plk3 (Polo-like kinase 3) as a novel DSB response factor that phosphorylates CtIP in G1 in a damage-inducible manner and impacts on various cellular processes in G1. First, Plk3 and CtIP enhance the formation of ionizing radiation-induced translocations; second, they promote large-scale genomic deletions from restriction enzyme-induced DSBs; third, they are required for resection and repair of complex DSBs; and finally, they regulate alternative NHEJ processes in Ku(-/-) mutants. We show that mutating CtIP at S327 or T847 to nonphosphorylatable alanine phenocopies Plk3 or CtIP loss. Plk3 binds to CtIP phosphorylated at S327 via its Polo box domains, which is necessary for robust damage-induced CtIP phosphorylation at S327 and subsequent CtIP phosphorylation at T847.

Journal or Publication Title: The Journal of cell biology
Volume: 206
Number: 7
Divisions: 10 Department of Biology
10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 14 Oct 2014 10:18
Export:

Optionen (nur für Redakteure)

View Item View Item